7-130276698-C-A

Variant names:

• chr7-130276698-C-A
• NM_001869.3:c.656C>A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001869.3(CPA2):​c.656C>A​(p.Pro219Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CPA2 NM_001869.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.38

Genes affected

CPA2 (HGNC:2297): (carboxypeptidase A2) Three different forms of human pancreatic procarboxypeptidase A have been isolated. The encoded protein represents the A2 form, which is a monomeric protein with different biochemical properties from the A1 and A3 forms. The A2 form of pancreatic procarboxypeptidase acts on aromatic C-terminal residues and is a secreted protein. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.974

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPA2	NM_001869.3	c.656C>A	p.Pro219Gln	missense_variant	Exon 7 of 11	ENST00000222481.9	NP_001860.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPA2	ENST00000222481.9	c.656C>A	p.Pro219Gln	missense_variant	Exon 7 of 11	1	NM_001869.3	ENSP00000222481.4
CPA2	ENST00000416698.1	n.*207C>A		non_coding_transcript_exon_variant	Exon 8 of 8	5		ENSP00000395582.1
CPA2	ENST00000487259.5	n.671C>A		non_coding_transcript_exon_variant	Exon 7 of 7	2
CPA2	ENST00000416698.1	n.*207C>A		3_prime_UTR_variant	Exon 8 of 8	5		ENSP00000395582.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460092 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726494

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.021	T
MetaRNN	Pathogenic	0.97	D
MetaSVM	Benign	-0.54	T
MutationAssessor	Pathogenic	4.1	H
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.33
Sift	Benign	0.036	D
Sift4G	Uncertain	0.040	D
Polyphen		1.0	D
Vest4		0.67
MutPred		0.93		Gain of sheet (P = 0.0827);
MVP		0.57
MPC		0.52
ClinPred		0.99	D
GERP RS		2.8
Varity_R		0.76
gMVP		0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-129916538;